Cleanser composition and methods for using the same

ABSTRACT

The present invention is directed to anti-microbial cleanser compositions comprising linalool, hinokitiol and dipropylene glycol. The present invention further provides methods for using these compositions to maintain eyelid hygiene, to treat an ocular disorder or to clean a skin surface. The cleanser compositions of the present invention can be in the form of a foam, gel or liquid.

RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.61/174,628, filed May 1, 2009, the entire contents of which are herebyincorporated herein by reference.

BACKGROUND OF THE INVENTION

Numerous opthalmologic diseases and disorders result from microbialovergrowth on the eyelid. The majority of these could be prevented ortreated by using a product that has the ability to remove dirt anddebris from the eyelid and surrounding area and, additionally, has theability to kill microorganisms, e.g., bacteria or yeast, that colonizethe area. Additionally, this product would have to be suitable forapplication to the eyelid and surrounding area.

Accordingly, the instant invention provides compositions and methods forcleaning the eyelid and/or skin surfaces.

SUMMARY OF THE INVENTION

The present invention is directed to novel compositions and methodseffective for decreasing microbial colonization on the eyelid. Themethods and compositions disclosed herein are useful for dailycleansing. These methods involve the easy and safe application of thecomposition to the eyelid in controlled doses effective for maintenanceof eyelid hygiene. The disclosed compositions are effective against abroad range of microbes that commonly colonize the eye and surroundingtissue.

Accordingly, the invention provides cleanser compositions suitable forapplication to the skin and ocular surface comprising linalool,hinokitiol and an alcohol. The alcohol can be a diol, such as a glycol.Exemplary glycols include propylene glycol, and ethylene glycol anddipropylene glycol.

The cleanser compositions of the invention may further comprise decylglucoside, sodium trideceth sulfate, cocamidopropyl betaine, dipropyleneglycol or mixtures thereof.

The cleanser compositions of the invention are suitable for directapplication to the ocular surface, an eyelid or the skin surrounding theeyelid of a subject.

The cleanser compositions of the invention can be applied as a foam, gelor liquid.

In exemplary embodiments, the cleanser compositions of the invention areuseful for the treatment of an ocular disorder, such as dry eye,excessive bacteria on the eyelid dermis, Meibomian gland dysfunction(MGD), blepharitis, acne rosacea, scalp dandruff, seborrheic dermatitis,chalazion, hordeolum, sty infectious conjunctivitis, corneal ulcer orany combination thereof. In specific embodiments, the ocular disorder isanterior or posterior blepharatis.

The cleanser compositions of the invention are effective against atleast one of the following microorganisms: S. aureus, P. aeruginosa, B.catarrhalis, E. coli, S. marcescens, S. epidermidis, MRSA, and P. ovale.Specifically, the compositions are effective against antibioticresistant bacteria such as methicillin resistant S. aureus.

Exemplified cleanser compositions of the invention contain the followingcomponents in approximately the following concentrations as a percent byweight:

(a) Coladet BSB 0.5-10.0%; (b) Decyl Glucoside 0.2-10.0%; (c) Linalool0.5-2.0%; (d) Cocamidopropyl PG-Dimonium 0.01-5.0%; Choloride Phosphate(e) Trisodium EDTA 0.01-1.0%; (f) Allantoin 0.01-1.0%; (g) Panthenol0.01-1.0%; (h) Hinokitiol 0.01-5.0%; (i) Tea Tree Oil 0.005-2.0%; (j)Vitamin E Acetate 0.005-2.0%; (k) Water 0.0-98.15%; (l) Dipropyleneglycol 1.0-50.0%; and (m) Cocamidopropyl betaine 0.1-20.0%.

A particular exemplified cleanser composition of the invention comprisesthe following components in approximately the following amounts as apercent by weight:

(a) Coladet BSB 3.8%; (b) Decyl Glucoside 1.7%  (c) Linalool 0.9%; (d)Cocamidoproply PG-Dimonium 0.2%; Choloride Phosphate (e) Trisodium EDTA0.1%; (f) Allantoin 0.1%; (g) Panthenol 0.1%  (h) Hinokitiol 0.05%; (i)Tea Tree Oil 0.025%; (j) Vitamin E Acetate 0.01%; (k) Water 68.215%; (l)Dipropylene glycol 23.0%; and (m) Cocamidopropyl betaine 2.0%.

Another specific composition of the invention is an opthalmologicallyacceptable cleanser composition comprising linalool, hinkokitiol andcocamidopropyl PG-dimonium chloride phosphate.

The cleanser compositions of the invention are in the pH range fromabout 4.5 to about 6.0, specifically from about 5.3 to about 5.7.

The invention also provides methods of cleaning a body surface of asubject by providing the cleanser composition described herein andapplying the cleanser composition to the surface; thereby cleaning thesurface.

The invention also provides methods of cleaning a body surface of asubject by providing a dispensing device containing the cleansercomposition described herein, dispensing an amount of the cleansercomposition from the dispensing device; and applying the foam to thesurface, thereby cleaning the surface.

In some methods, the compositions are in the form of a foam, gel orliquid. In other methods, the surface being treated is an eyelid.

The invention further provides methods of treating a subject having ademodex infestation, by applying a cleanser composition of the inventionto the eye lid, thereby treating the demodex infestation.

In the methods of the invention, the cleanser composition is formulatedsuch that upon application to the body surface or eyelid, the cleansercomposition does not substantially damage or irritate the body surfaceor eyelid.

In an exemplary method of the invention, the inventions provides amethod of treating ocular disorder in a subject by providing adispensing device containing the cleanser compositions described herein,dispensing an amount of the cleanser composition from the dispensingdevice in the form of foam, liquid or gel, and applying the compositionto the eye lid, thereby treating an ocular disorder. The method mayfurther comprise cleansing the eyelid by localized and sustainedmassaging of the composition.

The disclosed methods are useful for the treatment of, for example, dryeye, excessive bacterial colonization on the eyelid, Meibomian glanddysfunction (MGD), blepharitis, acne rosacea, scalp dandruff, seborrheicdermatitis, chalazion, hordeolum, sty, infectious conjunctivitis,corneal ulcer, demodex infestation, or any combination thereof. Inspecific exemplary methods, the oclar disorder is anterior blepharatisor posterior blepharitis.

The invention also provides devices for producing foam, wherein thedevice contains a cleanser composition suitable for application to theskin comprising linalool, hinokitiol and dipropylene glycol. Inexemplary embodiments of the invention, the cleanser composition isdispensed utilizing a device having a pump mechanism and a squeezemechanism and wherein the device delivers the foam to an applicator forapplication to the eyelid of the subject.

The invention also provides kits for maintaining eyelid hygiene in asubject comprising the cleanser composition of the invention or thedevices comprising the cleanser compositions, and instructions for use.The kits can further include an applicator, such as a sponge.

DETAILED DESCRIPTION OF THE INVENTION

As described herein, the inventors have invented highly effectivecompositions for cleansing the eye and the surrounding area, and fortreating ocular disorders. The inventors also set forth methods and kitsfor using these cleanser compositions.

DEFINITIONS

The invention will be described with reference to the followingdefinitions that, for convenience, are collected here.

The term “controlled concentration” is defined as a characteristic of amixture where the ratio of active ingredient(s) to non-activeingredient(s) is controllable at a prescribed level, and thereforedefinitive amounts of the mixture, and ingredients contained therein,can be delivered/distributed. Such a characteristic is useful inproviding controllable dosage regimens (i.e., improving predictabilityof the dose delivered).

The term “foam” is defined as a mass of bubbles of air or gas in amatrix of liquid, such as the compositions described herein. Foam can begenerated by any of the various methods know in the art.

The term “cleaning an eyelid” is used herein to describe the act ofsignificantly reducing the amount of microbes, dirt, debris, orotherwise undesired material from the eyelid and/or the area around theeye. In exemplary embodiments, the invention provides methods forcleansing the eye and surrounding areas and decreasing the colonizationof S. aureus, P. aeruginosa, B. catarrhalis, E. coli, S. marcescens, S.epidermidis, and P. ovale. In one embiodiment, the S. aureus aremethicillin resistant S. aureus.

The term “direct application” is used herein to describe the applicationof a cleanser composition to a subject, e.g., an eyelid or a surface,e.g., the skin, of a subject, with no additional processing orpreparation of the cleanser, e.g., no manual foaming or lathering, priorto application.

The term “dispensing” is defined as the act of delivering a cleansercomposition to an applicator that has not been stored in direct contactwith an applicator, e.g., in contrast to commercially available eyelidscrubs where the sponge is stored in direct contact with the cleanserliquid.

The term “dry eye” is known in the art as a condition of a subject thathas a lack of quality and/or quantity of tears. Dry eye is often anage-related disease. Meibomian gland dysfunction is a frequent cause ofdry eye and manifests itself in such forms as stenosis or closure of themeibomian gland orifices, inflammation of the meibomian glands, sty,hordeolum or other inflammation of the connective tissue. Meibomiangland dysfunction is commonly linked with ocular rosacea, blepharitis,and other inflammation of the eyelids. All of these causes ofinflammations of the skin are related to bacterial or yeast infection.

The term “eyelid” as used herein, includes the ocular surface mostcommonly the ocular surface, both the interior and exterior surfaces ofthe eyelid, the eyelid margin, the glands in and around the eyelidmargins, the hair follicles of the eye, the eyelashes, and theperiocular skin surrounding the eye.

The term “ocular disorder” is defined as a disorder of the eye that canbe treated or improved by cleansing the eyelids and/or eye of microbesand/or debris. Exemplary ocular disorders include, but are not limitedto, dry eye, excessive bacteria on the eyelid dermis linked to Meibomiangland dysfunction (MGD), blepharitis, acne rosacea, scalp dandruff,seborrheic dermatitis, chalazion, hordeolum, sty, infectiousconjunctivitis, corneal ulcers and any combination thereof.

The term “localized and sustained massaging”, as used herein, defines amanner of agitation of an eyelid of a subject. The massaging is focusedon the eyelid for an amount of time sufficient for cleaning an eyelidand surrounding areas, and results in significant agitation of theglands of the eyelid. This term is distinguishable from the incidentalagitation of the eyelid associated with, for example, washing the entireface including the eyelid. In certain embodiments, the massaging issustained for at least 5 seconds and possible for 30-60 seconds.

The term “sponge” as used herein includes all absorbent materials suchas pads, swabs, tissues, Q-tips, washcloths, or fiber applicators of anykind that may be used to induce foaming and/or used as an applicator foran eyelid cleanser.

The term “transiently stable foam” is used herein to define a foam thatmaintains its foam nature for a sufficient amount of time as to beuseful in the application to an eyelid of a subject. A transientlystable foam need not be present in the form of a foam indefinitely, butrather only as long as needed to provide a subject sufficient time toapply the dispensed foam to the eyelid.

The term “treatment” as used herein is defined as prophylactic treatment(e.g., daily preventative use) or therapeutic treatment (e.g., a singletreatment or a course of treatment) of a subject with an oculardisorder, which results in the reduction, alleviation, or elimination ofat least one symptom of an ocular disorder.

Methods And Compositions

Decreasing microbial overgrowth on the eyelids and surrounding tissuesis important for treating dry eye, blepharitis and for prophylaxis ofinfection prior to eye surgery. Patients with dry eye and blepharitishave microbial overgrowth on the eyelid skin. As such, the presentinvention is intended to emphasize the maintenance of eyelid hygienethrough prophylaxis in addition to treatment using the compositions andmethods of the present invention. The present methods, which involvelocalized and sustained massaging of the eyelids, assist in the removalof any overgrowth of common bacteria and yeast that cause inflammationof the eyelids and meibomian glands and pose a risk for those havingsurgery.

Accordingly, the invention provides cleanser compositions that aresuitable for direct application to an eyelid, or surrounding area, of asubject that are effective for maintaining eyelid hygiene. The cleansercomposition may be specifically formulated for the treatment of anocular disorder, e.g., an ocular disorder selected from those includingdry eye, excess bacteria on the eyelid dermis linked to Meibomian glanddysfunction (MGD), blepharitis, acne rosacea, scalp dandruff, seborrheicdermatitis, chalazion, hordeolum, sty or any combination thereof.

The cleanser compositions of the invention can also be used to cleanother skin surfaces, e.g., the hands or feet.

The cleanser compositions of the invention contain linalool, hinokitioland an alcohol, e.g., a diol such as glycol, e.g. diproplyene glycol.

More specifically, the cleanser compositions may contain one of more ofthe following components: linalool, hinokitiol, coladet BSB, decylglucoside, cocamidopropyl PG-dimonium chloride phosphate, cocamidopropylbetaine, trisodium ethylenediaminetetraacetic acid (trisodium EDTA),allantoin, panthenol, melaleuca alternifolia (Tea Tree) leaf oil,vitamin E acetate, citric acid, dipropylene glycol, and sodiumhydroxide.

Linalool is a naturally occurring terpene alcohol with broad spectrumantimicrobial properties. It has limited solubility in water and,therefore, a solubilizer must be added to increase the antimicrobialactivity of linalool. Suitable solubilizers include diol alcohols suchas, for example, ethylene glycol, propylene glycol, dipropylene glycol.In exemplary embodiments of the invention, the cleanser compositionscomprise between about 0.5 to about 2.0% linalool, between about 0.7 andabout 1.5% linalool or preferably about 0.9% linalool.

Hinokitiol is a tropolone alcohol with antimicrobial and antifungalactivity. It is particularly effective against the scalp dandruff or P.Ovale that is common in patients with seborrheic blepharitis. Inexemplary embodiments of the invention, the cleanser compositionscomprise between about 0.01 and about 5.0% hinokitiol, or between about0.02 and about 3.0% hinokitiol, or preferably about 0.05% hinokitiol.

Coladet BSB is surfactant blend intended to deliver very mild, gentlefoaming activity and is available from Colonical Chemical (Dalton, Ga.).When combined with decyl glucoside and cocamidopropyl betaine thesolution forms thick, dense and gentle foam. In exemplary embodiments ofthe invention, the cleanser compositions comprise between about 0.5 andabout 10.0% coladet BSB, between about 0.7 and about 7.0% coladet BSB,and preferably about 3.6% coladet BSB.

Decyl glucoside is a mild non-ionic surfactant. When used in combinationwith coladet BSB and cocamidopropyl betaine it results in improvedfoaming characteristics to create fuller, denser and thicker foam. Inexemplary embodiments of the invention, the cleanser compositionscomprise between about 0.2 and about 10% decyl glucoside, between about0.5 and about 4% decyl glucoside and preferably about 1.7% decylglucoside.

Cola® Lipid C, chemically described as cocamidopropyl PG-dimoniumchloride phosphate, is a coconut oil derived phospholipid composedpredominantly of diester and triester phosphatides with multiple chaingroups. In addition to topically simulating the properties displayed bythe polar stratum corneum lipids, Cola® Lipid C displays a broad rangeof functional attributes including gentle cleansing and foamingproperties, anti-irritation effects when combined with anionicsurfactants, unusually high substantivity, and long lasting skinconditioning, Cola® Lipid C is non-irritating to skin and eyes. Inexemplary embodiments of the invention, the cleanser compositionscomprise between about 0.01% and about 5% cocamidopropyl PG-dimoniumchloride phosphate, between about 0.1 and about 4% cocamidopropylPG-dimonium chloride phosphate, or preferably about 0.2% cocamidopropylPG-dimonium chloride phosphate.

Cocamidopropyl betaine is used as foam booster stabilizer to provideimproved foaming characteristics. Tegobetaine is a 35% minimum activesolution of cocamidopropyl betaine. Other betaines, e.g., sultaines, mayalso be used. In exemplary embodiments of the invention, the cleansercompositions comprise between about 0.1 and about 20% cocamidopropylbetaine, between about 0.5 to about 10% cocamidopropyl betaine orpreferably about 2.0% cocamidopropyl betaine.

Trisodium ethylenediaminetetraacetic acid (EDTA) is. Other protonatedforms EDTA may be substituted for trisodium EDTA. In exemplaryembodiments of the invention, the cleanser compositions comprise betweenabout 0.01 to about 1.0% trisodium EDTA, between about 0.2 to about 0.7%trisodium EDTA or preferably about 0.1% trisodium EDTA.

Allantoin is used as a skin healer. It increases the smoothness of theskin; promotion of cell proliferation and wound healing; and has asoothing, anti-irritant, and skin protectant effect by forming complexeswith irritant and sensitizing agents. In exemplary embodiments of theinvention, the cleanser compositions comprise between about 0.01 toabout 1.0% allantoin, about 0.05 to about 0.7% allantoin, or preferablyabout 0.1% allantoin.

Panthenol is the alcohol analog of pantothenic acid (vitamin B5).Panthenol functions as a moisturizer, humectants and emollient.Panthenol (dL panthenol) improves hydration, reduces itching andinflammation of the skin and accelerates and improves healing ofepidermal wounds. In exemplary embodiments of the invention, thecleanser compositions comprise between about 0.01 to about 1.0%panthenol, about 0.05 to about 0.7% panthenol, or preferably about 0.1%panthenol.

Melaleuca Alternifolia (Tea Tree) leaf oil is a natural antifungal andantibacterial composition. It is effective against nail fungus,ringworm, athlete's foot, dandruff, acne and many types of infestationsincluding lice, mites and scabies. Tea tree oil is not just soothing anddisinfecting, it is capable of penetrating into the lower skin layerswith its anti-inflammatory, disinfectant, pain killing and wound healingqualities. In exemplary embodiments of the invention, the cleansercompositions comprise between about 0.005 and 2.0% MelaleucaAlternifolia (Tea Tree) leaf oil, and preferably about 0.025% MaleleucaAlternifolia (Tea Tree) leaf oil.

Vitamin E acetate is an antioxidant, possessing the ability to increasethe moisturization of the skin. In addition to the properties related toskin moisturization and maintenance, vitamin E acetate is alsoantioxidant to linalool. In exemplary embodiments of the invention, thecleanser compositions comprise between about 0.005 and about 1.0%vitamin E acetate, between about 0.008 and about 0.5% vitamin E acetate,or preferably about 0.01% vitamin E acetate.

Dipropylene Glycol (DPG LO+) provides excellent co-solvency for water,oils and hydrocarbons, with minimal odor, low skin irritation potential,low toxicity and consistent isomer distribution, making it ideal for usein pharmaceutical and personal care products. Other low diols such aspropylene glycol and ethylene glycol may be used. In exemplaryembodiments of the invention, the cleanser compositions comprise betweenabout 1 and about 50% dipropylene glycol, between about 5 and about 40%dipropylene glycol or preferably about 23.0% dipropylene glycol.

Acids and bases, such as citric acid and sodium hydroxide can be used toadjust the pH of the composition to the desired range, e.g., near thephysiologic pH of the skin, 4.5-6.0 or preferably 5.3-5.7.

In exemplary embodiments, the invention provides a opthopthalmologicallyacceptable cleanser composition comprising the following components inthe following range of concentrations:

(a) Coladet BSB 0.0-10.0%; (b) Decyl Glucoside 0.2-10.0%; (c) Linalool0.5-2.0%; (d) Cocamidoproply PG-Dimonium 0.01-5.0%; Choloride Phosphate(e) Trisodium EDTA 0.01-1.0%; (f) Allantoin 0.01-1.0%; (g) Panthenol0.01-1.0%; (h) Hinokitiol 0.01-5.0%; (i) Tea Tree Oil 0.005-2.0%; (j)Vitamin E Acetate 0.005-2.0%; (k) Water 0.0-98.15%; (l) DipropyleneGlycol 1.0-50.0%; and (m) Cocamidopropyl Betaine 0.1-20.0%;

In a further exemplary embodiment, the invention provides aopthopthalmologically acceptable cleanser composition comprising thefollowing components at about the following concentrations:

(a) Coladet BSB 3.6%; (b) Decyl Glucoside 1.7%  (c) Linalool 0.9%; (d)Cocamidopropyl PG-Dimonium 0.2%; Choloride Phosphate (e) Trisodium EDTA0.1%; (f) Allantoin 0.1%; (g) Panthenol 0.1%  (h) Hinokitiol 0.05%; (i)Tea Tree Oil 0.025%; (j) Vitamin E Acetate 0.01%; (k) Water 68.215%; (l)Dipropylene Glycol 23.0%; and (m) Cocamidopropyl Betaine 2.0% 

The invention is further directed to a method of cleaning an eyelid of asubject or to treat ocular disorder in a subject. The method comprisesthe steps of providing a cleanser composition, dispensing the cleansercomposition, applying the composition to the eyelid, and, optionally,agitating the eyelid by localized and sustained massage of thecomposition onto the eyelid. The composition maybe dispensed onto afingertip or an applicator device such as a sponge. The subject in needof treatment may have been diagnosed previously with an ocular disorder.

The invention is further directed to a method of cleaning a surface,e.g., skin surface, e.g. a skin surface, of a subject. The methodcomprises the steps of providing a cleanser composition, dispensing thecleanser composition; applying the composition to the surface andoptionally agitating the surface. The composition maybe dispensed onto afingertip or an applicator device such as a sponge. The subject in needof treatment my have been diagnosed previously with an ocular disorder.

The invention also provides methods of cleaning the eyelid using thecleanser composition in the form of a foam. The method comprises thesteps of providing a cleanser composition, dispensing the cleansercomposition in the form of a foam, applying the foam to the eyelid, and,optionally, agitating the eyelid by localized and sustained massage ofthe foam onto the eyelid. The foam maybe dispensed onto a fingertip andthe fingertip is used to agitate the eyelid. The subject in need oftreatment may have been diagnosed previously with an ocular disorder.

Furthermore, the dispensing apparatus may deliver foam to an applicator,e.g., a finger, utilizing a pump mechanism or a squeeze mechanism. Itwould also be understood by the ordinarily skilled artisan that themethods described above may utilize the foam in combination with anymechanical cleaning technique, for example, commercially availableeyelid pads or scrubs.

The cleanser composition of the invention may be in the form of aliquid, gel or a foam. The cleanser composition may be any aqueoussolution that can be formulated to form, provided that the compositionis not significantly deleterious to the comfort or health of the eyeand/or detracts from the compliance of use. For example, the cleansercomposition may be an aqueous formulation formulated with sufficientadditives to produce a stable foam from a dispenser engineered toproduce a foam.

In certain embodiments of the invention, the cleanser composition can bedispensed from a dispensing apparatus. In one embodiment, the dispensingapparatus can be any device that delivers a cleanser composition in theform of a foam. However, it should be understood that, in contrast tocommercially available eyelid scrubs where the sponge is stored indirect contact with the cleanser liquid, a dispenser useful in themethods of the invention is one in which the cleanser composition, e.g.,cleanser composition of the present invention, is not stored in directcontact with an applicator. For example, the dispensing apparatus may bea device that has a container portion for containing the liquid cleansercomposition (or liquid cleaning agent and a separately contained aqueousportion), an induction spout that acts to thaw the liquid cleanser fromthe container upon actuation, and a foaming portion attached to theinduction spout that creates a controlled concentration foam from theliquid composition received from the induction spout. The inductionspout may be actuated by a pump or a squeeze mechanism. A preferreddispenser is an airless foamer, e.g. a mini-airless foamer.

The cleanser compositions of the invention may include any aqueoussolution that contains surfactants or additives with surfactant-likebehavior

The compositions of the invention may be used one or more time per day,or as directed by a doctor.

The cleanser compositions may be formulated so that application to theeyelid does not substantially damage the skin of the eyelid, even withfrequent, e.g., twice daily, application. Furthermore, the cleansercompositions of the invention may be formulated for any desiredproperty, e.g., substantially non-irritating, maintenance of pH of theeyelid skin, improved ability to remove dirt and debris, and/or toincrease the stability of the controlled concentration foam.

The cleanser can be formulated as a liquid, gel or foam. The liquid formmay be added with a moistened pad or sponge. The gel form can be appliedwith a pad or sponge as well as delivered with the fingers. The gel hasthe advantage that it will not drain between the fingers.

The foam form may be prepared by generating a foam from an aqueoussolution that contains sufficient additives, e.g., surfactants oradditives with surfactant-like behavior, to produce a foam that isstable. The foam provides a standardized, substantially invariable, andpredefined amount of cleaning agent in a given amount of foam thus,improving the dosing regimen for maintaining eyelid hygiene. Moreover,once generated, the foam is suitable for application directly to theeyelid of subject, with the fingers, with the advantage that it does notdrain between the fingers as a liquid with the advantage that the doseof the cleaning agent is well-defined, i.e., controlled, to assist inthe process of accurate prescription. Additionally, the chosen dilutionratio may be customized based on the desired application, i.e., moreconcentrated for applications that require increased/enhanced cleaning.

The foam should be transiently stable in order to be useful. The foamneed not be present in the form of a foam indefinitely; rather, the foamneeds to be stable only as long as needed to provide a subjectsufficient time to apply the dispensed foam to the eyelid. The stablefoam is useful in gently removing dirt and debris from the eyelid andpenetrating between the eyelashes and into the hair follicle, which areknown to catch debris. Additionally, a stable foam which is appliedindependent of a sponge applicator contributes to the improvedeffectiveness of the present invention by introducing the step ofmassaging the eyelid with the fingers, which is more beneficial for themaintenance of skin integrity than the use of abrasive scrubbing.

Application of the composition to the eyelid or a surface of a subjectmay be by self-administration or by a trained professional, e.g., adoctor. More importantly, the application of the composition may bedirect; e.g., it may be applied with a fingertip directly to the eyelidsfor blepharitis or to the ocular surface for the treatment of aninfectious conjunctivitis or corneal ulcer.

In contrast to known methods which involve manual foaming or lathering,either with or without the agitation of a sponge, the foam presentinvention requires no additional processing or preparation of thecleanser prior to application to the eyelid. The advantage ofeliminating this processing step ensures the presence of a standardizedamount of cleaning agent in the resulting foam, i.e., the use of acontrolled concentration foam.

Agitating the eyelid of surface by localized and sustained massaging ofthe composition improves the removal of dirt and debris as compared withknown methods. Massaging is sustained for a period of time sufficient tosubstantially stimulate the cleaning of the eye or surface. For example,the massaging may be maintained for at least 5-60 seconds.

The method of cleaning an eyelid or surface may further include arinsing step. This step preferably comprises a simple water rinse. Thecomposition may be rinsed with ample water after application and massageby bringing ample water to eyelid and eyelashes, e.g., with a hand,finger or any container suitable for this purpose.

The methods of the invention are not meant to only work in isolation.The method of cleaning may also include a wiping step in lieu of rinsingstep. The composition may be wiped off with a clean tissue, for example.More particularly, this invention provides a kit containing a productuseful for cleaning an eyelid, optionally packaged with additionalinstructions for use in maintaining eyelid hygiene or treating an oculardisorder in conjunction with the kits of the present invention.

The methods and compositions of the invention find numerous commercialapplications that could beneficially utilize the methods andcompositions for eyelid hygiene, treatment or prevention or oculardisorders, or cleansing of a surface, e.g., a skin surface.Consequently, the invention includes a kit comprising a cleansercomposition of the invention and instructions for use. In oneembodiment, the kit includes a dispenser that is capable of generating afoam The kit may further comprise an applicator, e.g., a sponge.

EXEMPLIFICATION OF THE INVENTION

The present invention may be further illustrated by the followingnon-limiting examples.

Example 1 An Exemplary Formulation of the Invention

Ingredients (INCI) Weight % Purified Water 68.215 Dipropylene Glycol23.0 Cocamidopropyl Betaine 2.0 Coladet BSB 3.6 (Blend of mildsurfactants - Peg-80 Sorbitan Laurate, Sodium Trideceth Sulfate,Cocamidopropyl Betaine Sodium Lauroamphoacetate, PEG-150 Distearate,Sodium Laureth-13 Carboxylate) Decyl Glucoside 1.7 Linalool 0.9Cocamidopropyl PG-Dimonium 0.2 Chloride Phosphate Trisodium EDTA 0.1Allantoin 0.1 Panthenol 0.1 Hinokitiol 0.05 Melaleuca Alternifolia 0.025(Tea Tree) Leaf Oil Vitamin E Acetate 0.01 Citric Acid 0.1(max if neededfor pH adjust.) Sodium Hydroxide 0.2(max if needed for pH adjust)

Protocol for Manufacturing

The above compositions were made in the following manner Each componentwas individually added to a vessel containing water at room temperatureand mixed until uniform. If needed, the formulas are adjusted tophysiological skin pH with citric acid or sodium hydroxide. Theresulting preparation is a clear, single phase solution. Eachpreparation was prepared in this same manner The component amounts givenin the tables are expressed as percent by weight.

Experimental Design

A suspension of bacterial cells was exposed to the test substance forspecified contact times. After exposure, an aliquot of the suspensionwas transferred to a neutralizing structure media and assayed forsurvivors. Appropriate purity, subculture medium sterility,microorganism population and neutralization controls were performed.

Test Exposure: 30 seconds and 60 seconds

Exposure Temperature Room temperature (21.0-23 C)

Soil Load Description: No Organic soil load

Dilution: Ready to Use (RTU)

Recovery Media:

Neutralizing Subculture Medium: Letheen Broth+2.0% Lecithin+2.0% Tween80

Efficacy Data Test Population Control Number of Log₁₀ Exposure (CFU/mL)*Survivors Number of Percent Log₁₀ Test Organism Time Log₁₀ (CFU/mL)*Survivors Reduction Reduction Staphylococcus 30 seconds 9.4 × 10⁵ 2.39 ×10⁴  4.378 97.5% 1.59 aureus 60 seconds 5.97 9.0 × 10³ 3.95 99.0% 2.02Pseudomonas 30 seconds 3.8 × 10⁶ <2 <0.3 >99.9999% >6.3 aeruginosa 60seconds 6.58 <2 <0.3 >99.9999% >6.3 Moraxella 30 seconds 1.45 × 10⁶  <2<0.3 >99.99% >4.9 (Branhamella) 60 seconds 5.161 <2 <0.3 >99.99% >4.9catanhalis Escherichia coli 30 seconds 5.0 × 10⁵ <2 <0.3 >99.999% >5.460 seconds 5.70 <2 <0.3 >99.999% >5.4 Serratia 30 seconds 1.48 × 10⁶ 1.1 × 10² 2.04 99.99% 4.13 marcescens 60 seconds 6.170 <2<0.3 >99.999% >5.9 Staphylococcus 30 seconds 8.1 × 10⁵ 6.5 × 10³ 3.8199.2% 2.10 epidermidis 60 seconds 5.91 2.05 × 10³  3.312 99.7% 2.60Staphylococcus 30 seconds 1.53 × 10⁶  2.04 × 10²  2.310 99.9% 3.875aureus - MRSA 60 seconds 6.185 4.8 × 10¹ 1.68 99.99% 4.51 Pityrosporum30 seconds 3.1 × 10³ 4.24 × 10²  2.627 86.3% 0.86 ovale 60 seconds 3.491.3 × 10² 2.11 95.8% 1.38 *colony forming units per mL of test mixture

Example 2 Efficacy of Formulations Against Demodex Mites

The goal of this example was to determine if the formulations of theinvention are effective for killing Demodex mites.

Materials. Control 50% baby shampoo, 5% Formula as Set forth in Example1, 5% Tea Tree Oil (TTO), 50% TTO

Methods. Patients who exhibited cylindrical sleeves on their lashes wereselected and a slit lamp exam was performed to determine which lasheswould be epilated. The lashes were then immersed in an agent andexamined with a light microscope. The presence of Demodex was determinedand the amount of time for the agent to completely kill the Demodex mitewas noted. Kill time was determined by the cessation of leg movements ofthe mites for a period of 10 minutes.

Results. Demodex survived for more than 180 minutes in 50% baby shampoo.In contrast, the mean survival time for Demodex immersed in 50% TTO, 5%TTO, and the formulation set forth in Example 1 ranged from 8 minutes(50% TTO) to 51 minutes (formulation set forth in Example 1).

Anterior blepharitis is an inflammation of the eyelids that causesredness, irritation, an itchy sensation, and the formation ofdandruff-like scales on eyelashes. It involves the irritation of theouter front edge of the eyelid where the eyelashes are attached. Manycauses of anterior blepharitis have been described, but this study isparticularly concerned with ocular Demodex infestation.

Patients with anterior blepharitis often present with cylindricaldandruff on their eyelashes. Cylindrical dandruff (CD) are scales thatform clear cuff collars around eyelash roots. This is often indicativeof the presence of ocular Demodex because it is regarded aspathognomonic of Demodex infestation.

Materials

50% Johnson and Johnson baby shampoo

5% Tea Tree Oil (TTO)

the formulation set forth in Example 1

Methods

Patients were selected, who displayed evidence of anterior blepharitis.A slit lamp was used to examine the patient population to determine thatthose selected evinced cylindrical dandruff around at least 8 eyelashes.Based on previous studies, cylindrical dandruff on 8 eyelashes issufficient to indicate a modest infestation of ocular Demodex. Thepatient selection was not exclusive based on age, ethnicity, or gender.The only patients excluded from the study were those who were currentlyon a tea tree oil treatment regimen or those who had undergonefluorescent staining.

One affected eyelash from each fourth of the upper eyelids was epilatedusing jeweler's type forceps and a slit lamp microscope (Nikon, DiaScopeII, Japan).

Two individual eyelashes were placed on each microscope slide andimmediately saturated with 20 μL of a blindly selected test solution. Aplastic coverslip was then placed over the mixture and the slide wasexamined. Under the microscope, we searched for the presence of livingadult Demodex.

Confirmation of the mites' live status was evidenced by vigorousmovement of their four pairs of legs. Adult Demodex is distinguishablefrom juvenile Demodex because of its well formed legs, stumpy body, andlength of approximately 0.4 mm.

Once the determination was made that mites were present and alive on theslides, mitesw were observed every 10 minutes to check for obvious signsof reduction of leg movement. When it became apparent that only one ofits legs was moving irregularly, the mite under observation was watchedcontinuously until its leg ceased to move.

Observation was continued for a period of 10 additional minutesfollowing the cessation of leg movement in order to establish theaccuracy of our recorded kill time. Kill time is calculated as the timebetween exposure of the mite to the agent and cessation of mite legmovement for a period longer than 10 minutes.

Solutions in which Demodex immersion did not result in death after 180minutes were assumed to be ineffective and observation was discontinued.Demodex were excluded from the study if they did not have vigorous legmovements at the beginning of observation, or if more than half of theirbodies were encased in cylindrical dandruff.

Results

TABLE 1 Resultant mean kill time of the test agents that successfullykilled the Demodex before 180 minutes 50% Formulation Baby 5% of ShampooTTO Example 1 Mean >180 14.000 51.429 kill time (minutes) # of 20 17 21Demodex

Discussion

In this in vitro study of the effects of applying topical and eyelidcleansing agents to Demodex derived from patients with anteriorblepharitis, it was determined that only 5% TTO and the formulation setforth in Example 1 were effective in eradicating the mites in a timelymanner. 50% TTO was able to kill the Demodex in approximately 8 (5.6)minutes, 5% TTO in 14 (7.3) minutes, and the formulation set forth inExample 1 in 51 (25.7) minutes. 50% baby shampoo was unable to killmites within a period of 180 minutes.

Although it is understood that TTO is a very effective cleansing agent,its use among patient populations may not be as high as expected becauseTTO acts as an irritant if it enters a patient's eyes.

Accordingly, the formulation set forth in Example 1 is effective fortreating subjects having a demodex infestation of the eye.

1. A cleanser composition suitable for application to the skin andocular surface comprising linalool, hinokitiol and an alcohol.
 2. Thecleanser composition of claim 1, wherein the alcohol is a diol.
 3. Thecleanser composition of 2, wherein the diol is a glycol.
 4. The cleansercomposition of claim 3, wherein the glycol is selected from the groupconsisting of propylene glycol, and ethylene glycol and dipropyleneglycol.
 5. The cleanser composition of claim 1, further comprising decylglucoside, sodium trideceth sulfate, cocamidopropyl betaine, dipropyleneglycol or mixtures thereof.
 6. The cleanser composition of claim 1,wherein the cleanser composition is suitable for direct application tothe ocular surface, an eyelid or the skin surrounding the eyelid of asubject.
 7. The cleanser composition of claim 1, wherein the cleansercomposition is a applied as a foam, gel or liquid.
 8. The cleansercomposition of claim 1, wherein the composition is for the treatment ofan ocular disorder.
 9. The cleanser composition of claim 8, wherein theocular disorder is selected from the group consisting of dry eye,excessive bacteria on the eyelid dermis, Meibomian gland dysfunction(MGD), blepharitis, acne rosacea, scalp dandruff, seborrheic dermatitis,chalazion, hordeolum, sty infectious conjunctivitis, corneal ulcer,demodex infestation, and any combination thereof.
 10. The cleansercomposition of claim 1, wherein the ocular disorder is anterior orposterior blepharatis.
 11. The cleanser composition of claim 1, whereinthe composition is effective against at least one of the followingmicroorganisms: S. aureus, P. aeruginosa, B. catarrhalis, E. coli, S.marcescens, S. epidermidis, MRSA, and P. ovale.
 12. The cleansercomposition of claim 11, wherein the S. aureus is methicillin resistantS. aureus.
 13. The cleanser composition of claim 1, wherein the cleansercomprises the following components in approximately the followingconcentrations as a percent by weight: (a) Coladet BSB 0.5-10.0%; (b)Decyl Glucoside 0.2-10.0%; (c) Linalool 0.5-2.0%; (d) CocamidopropylPG-Dimonium 0.01-5.0%; Choloride Phosphate (e) Trisodium EDTA 0.01-1.0%;(f) Allantoin 0.01-1.0%; (g) Panthenol 0.01-1.0%; (h) Hinokitiol0.01-5.0%; (i) Tea Tree Oil 0.005-2.0%; (j) Vitamin E Acetate0.005-2.0%; (k) Water 0.0-98.15%; (l) Dipropylene glycol 1.0-50.0%; and(m) Cocamidopropyl betaine 0.1-20.0%.


14. The cleanser composition of claim 9, wherein the cleanser comprisesthe following components in approximately the following amounts as apercent by weight: (a) Coladet BSB 3.8%; (b) Decyl Glucoside 1.7%  (c)Linalool 0.9%; (d) Cocamidoproply PG-Dimonium 0.2%; Choloride Phosphate(e) Trisodium EDTA 0.1%; (f) Allantoin 0.1%; (g) Panthenol 0.1%  (h)Hinokitiol 0.05%; (i) Tea Tree Oil 0.025%; (j) Vitamin E Acetate 0.01%;(k) Water 68.215%; (l) Dipropylene glycol 23.0%; and (m) Cocamidopropylbetaine 2.0%.


15. The cleanser composition of claim 1, wherein the pH range is about4.5-6.0.
 16. The cleanser composition of claim 1, wherein the pH rangeis about 5.3-5.7.
 17. A opthalmologically acceptable cleansercomposition comprising linalool, hinkokitiol and cocamidopropylPG-dimonium chloride phosphate.
 18. A method of cleaning a body surfaceof a subject comprising: applying the a cleanser composition set forthin claim 1 to the body surface; thereby cleaning the surface.
 19. Themethod of claim 18, wherein the composition is in the form of a foam,gel or liquid.
 20. The method of claim 18, wherein the surface is aneyelid.
 21. The method of claim 18, wherein the cleanser composition isformulated such that upon application to the body surface or eyelid thecleanser composition does not substantially damage or irritate the bodysurface or eyelid.
 22. A method of treating ocular disorder in a subjectcomprising the steps of: applying the cleanser composition to the ofclaim 1 to an eye lid; thereby treating an ocular disorder.
 23. Themethod of claim 22, further comprising cleansing the eyelid by localizedand sustained massaging of the composition.
 24. The method of claim 22,wherein the ocular disorder is selected from the group consisting of dryeye, excessive bacterial colonization on the eyelid, Meibomian glanddysfunction (MGD), blepharitis, acne rosacea, scalp dandruff, seborrheicdermatitis, chalazion, hordeolum, sty, infectious conjunctivitis,corneal ulcer, demodex infestation and any combination thereof.
 25. Themethod of claim 24, wherein the ocular disorder is anterior blepharatisor posterior blepharitis.
 26. A method of treating a subject having ademodex infestation, comprising the steps of: applying a cleansercomposition set forth in claim 1 to the eye lid; thereby treating ademodex infestation.
 27. The method of claim 26, wherein the cleansercomposition is the cleanser composition set forth in claim
 14. 28. A kitfor maintaining eyelid hygiene in a subject comprising the cleansercomposition of claim 1 and instructions for use.
 29. The kit of claim28, further comprising an applicator.
 30. The kit of claim 29, whereinthe applicator is a sponge.